Evidence suggests that airway smooth muscle, the most important cell modulating bronchomotor tone, plays an important immunomodulatory role in the orchestration and perpetuation of airway inflammation. The signaling pathways that modulate leukocyte function may be disparate from those found in resident effector cells such as airway smooth muscle, fibroblasts, and epithelial cells. Further investigation and understanding of the pivotal signaling pathways that modulate airway smooth muscle cell release, secretion of chemokines/cytokines, and expression of cell adhesion molecules may offer new therapeutic approaches in the treatment of asthma.